RESUMO
We integrated genetic risk scores (GRS) and environmental factors for identifying high-risk subjects for oral squamous cell carcinoma (OSCC) occurrence by using case-control study. A total of 447 patients diagnosed with OSCC and 580 unrelated subjects were recruited from two medical centers in Taiwan. A multinomial logistic regression model was conducted to access interaction between GRS and betel quid (BQ) chewing. We employed ROC curve to compare the accuracy of OSCC occurrence. Four tag SNPs were found in NOTCH1, BRCA1, COL9A1, and HSPA13 genes that were significantly associated with OSCC occurrence. GRS was calculated by the four tag SNP risk alleles. The higher GRS (scores = 4) remained independently associated with risk of OSCC after adjustment for age, the use of alcohol, BQ, and cigarette: adjusted OR = 4.42 [95% confidence interval (95% CI), 1.34-14.55]. The GRS and BQ chewing interaction showed an increased risk for OSCC occurrence with adjusting for other substance use and age (OR = 70.77; 95% CI, 8.70-575.73). The synergy index was 16.58 (95% CI, 2.27-70.56), suggesting a positive additive interaction between GRS and BQ chewing. The areas under the ROC curves (AUROC) were 0.91 for combined GRS and BQ chewing with sensitivity of 88.6% and specificity of 86.7%. The AUROC of GRS and BQ chewing is above 90%, which may be valuable in identifying high-risk subjects. Early screening can allow the clinician to provide the appropriate intervention and to reduce the OSCC occurrence. Cancer Prev Res; 10(6); 355-62. ©2017 AACR.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Neoplasias Bucais/genética , Piper betle/efeitos adversos , Extratos Vegetais/efeitos adversos , Adulto , Idoso , Proteína BRCA1/genética , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/prevenção & controle , Estudos de Casos e Controles , Colágeno Tipo IX/genética , Detecção Precoce de Câncer/métodos , Feminino , Proteínas de Choque Térmico HSP70/genética , Humanos , Modelos Logísticos , Masculino , Mastigação , Pessoa de Meia-Idade , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/prevenção & controle , Polimorfismo de Nucleotídeo Único , Curva ROC , Receptor Notch1/genética , Medição de Risco/métodos , Fatores de Risco , Taiwan/epidemiologiaRESUMO
Type IX collagen is one of the important components, together with type II, V, and XI collagens, in the tectorial membrane of the organ of Corti. To confirm the significance of type IX collagen for normal hearing, we assessed the detailed morphological and electrophysiological features of type IX collagen knock-out mice, which have recently been reported as a deafness model. Through assessment by auditory brainstem response (ABR), knock-out mice were shown to have progressive hearing loss. At the light microscopic level, the tectorial membrane of knock-out mice was found to be abnormal in shape. These morphological changes started in the basal turn and were progressive toward the apical turn. Electron microscopy confirmed disturbance of organization of the collagen fibrils. These results suggest that mutations in type IX collagen genes may lead to abnormal integrity of collagen fibers in the tectorial membrane.